ALS News Today brought you daily coverage of key findings, treatment developments, clinical trials, and other important events related to amyotrophic lateral sclerosis (ALS) throughout 2020, a year marked by the COVID-19 pandemic.
As a reminder of what mattered most to you in 2020, here are the top 10 most-read articles of last year with a brief description of what made them interesting and relevant to the ALS community.
We look forward to reporting more relevant news to patients, family members, and caregivers dealing with ALS throughout 2021.
A team of researchers in Germany found that caffeine and nicotinamide adenine dinucleotide in its oxidized form (NAD+) — two powerful antioxidants — improved the health of lab-grown motor neurons derived from a mouse model of sporadic ALS.
These benefits, seen in cells derived from mice either in a progressive or a stable disease state, were likely associated with a reduction in oxidative stress, a known contributor to sporadic ALS.
Of note, motor neurons, the specialized nerve cells that control voluntary movement, are progressively lost in people with ALS. Oxidative stress is an imbalance between the natural production of potentially harmful reactive oxygen species and the ability of cells to detoxify them with antioxidant agents.
In an April story, we reported AB Science’s plans to launch a Phase 3 clinical trial (NCT03127267) testing its experimental oral therapy masitinib as an add-on treatment for people with ALS, after the U.S. Food and Drug Administration (FDA) cleared its request for this study.
Masitinib is designed to block the activity of multiple cell types involved in the inflammatory and neurodegenerative processes marking ALS.
The study aims to assess whether add-on treatment with masitinib is superior to placebo at slowing functional decline in up to 495 ALS patients diagnosed in the past two years. Participants’ functional abilities will be assessed through the ALS functional rating scale-revised (ALSFRS-R). Both masitinib and placebo will be given in combination with Sanofi’s Rilutek (riluzole), an approved ALS medication.
The trial is currently recruiting patients at a single U.S. clinical site (Johns Hopkins in Maryland), but another site in Ulm, Germany, is expected to open shortly. Should study findings be positive, they are expected to support future requests for regulatory approval of masitinib as an ALS treatment.
No. 8 – “Mitochondrial ‘Suicide’ May Signal Start of Neurodegeneration in ALS, Mouse Study Suggests”
Using different mouse models of ALS, a team of researchers in the U.S. discovered a self-destructive mechanism in mitochondria — the cells’ powerhouses — that may be one of the first triggers of motor neuron degeneration in ALS.
This mitochondrial “suicide” was found only in the upper motor neurons — those that send messages from the brain to the spinal cord, and whose degeneration is thought to be an early disease event — of ALS mice, and before any signs or symptoms of the disease were evident.
These findings suggest that currently available therapies targeting mitochondrial degeneration may help to stop neurodegeneration in ALS, supporting further research in this area.
In July, BrainStorm Cell Therapeutics announced that all ALS patients enrolled in a pivotal Phase 3 clinical trial (NCT03280056) testing NurOwn, its investigational cell-based therapy, had completed dosing.
NurOwn involves expanding and maturing mesenchymal stem cells (MSCs) collected from a patient’s own bone marrow into cells that produce high levels of molecules promoting nerve cell growth and survival. MSCs are stem cells that can generate a variety of other cell types.
The mature cells — called MSC-NTF cells — are then injected into the patient’s spinal canal to promote and support nerve cell repair.
In the U.S.-based trial, 189 patients with rapidly progressing ALS were randomly assigned to either a total of three injections of either NurOwn, or a placebo, given directly into the spinal canal every other month.
The study’s main goal was to assess the therapy’s safety, and whether treatment was superior to placebo at slowing disease progression — as measured by the ALSFRS-R — at seven months following the first dose.
A couple of months earlier, we reported the results of a preclinical study suggesting that NurOwn may not only boost nerve cell protection and repair, but also suppress the damaging immune responses that contribute to ALS progression by promoting a shift toward an anti-inflammatory state.
BrainStorm researchers found that growing healthy B-cells and T-cells — immune cells known to be involved in ALS — in the lab with NurOwn suppressed the growth of pro-inflammatory cell subsets, and lowered the levels of pro-inflammatory molecules. At the same time, the therapy increased the numbers of immunosuppressive cell subsets and the levels of a major anti-inflammatory molecule.
BrainStorm announced in June that patient dosing in its Phase 3 trial evaluating NurOwn in people with ALS remained on track, despite occasional treatment scheduling changes due to the COVID-19 pandemic.
The company attributed the trial’s successful advancement during the pandemic to coordination among its six U.S. clinical sites, support and guidance from the FDA, and the fact that its main goal — based on the ALSFRS-R — could be assessed by phone.
Top-line data were shared before the year’s end, as anticipated by BrainStorm, and are under review by the FDA.
In April, ALS News Today reported on Seneca Biopharma’s plans to launch a Phase 3 clinical trial to assess the safety and effectiveness of NSI-566, its leading stem cell treatment candidate, in adults with ALS.
The decision was supported by previous positive data from a Phase 1 (NCT01348451) and Phase 2 (NCT01730716) clinical trial and a meeting with the FDA that provided guidance on how to best design and conduct the upcoming late-stage trial.
NSI-566 treatment involves the injection of fetal spinal cord stem cells into a patient’s spinal cord, where they mature into nerve cells that surround and support motor neurons. These mature cells also produce certain molecules that promote motor neuron growth and survival.
Results from the previous studies confirmed NSI-566’s safety, and suggested that the therapy may help to prevent further functional decline in ALS patients, when compared with data from other ALS trials.
A small study in Italy suggested that creatinine kinase — a marker of muscle damage — could be used as a biomarker to predict the rate of disease progression in people with ALS.
By analyzing this enzyme in 126 ALS patients, the researchers found that creatinine kinase levels were significantly higher in people with slow progressing disease compared with those with fast progressing disease, and that these differences were sustained over time.
Further analyses in mouse models of ALS confirmed these findings, and suggested that the slow progression was associated with greater muscle mass and a better ability to counter disease mechanisms for longer periods.
Elevated creatinine kinase blood levels also seemed to be specific to ALS among neurodegenerative diseases, suggesting that the muscle may be a therapeutic target in ALS.
No. 2 – “Kadimastem Finishes Treating Second Group of ALS Patients with AstroRx in Phase 1/2a Trial”
AstroRx delivers healthy, mature astrocytes derived from human embryonic stem cells to a patient’s spinal cord to compensate for diseased astrocytes and to prevent motor neuron loss. Astrocytes are star-shaped cells that normally support and protect nerve cells, but are abnormal in ALS.
Data from the first group of patients given the lowest therapy dose showed that the treatment was safe and slowed the rate of disease progression over the first three to four months following dosing. Results from the second group (given a higher dose) went on to confirm these promising three-month findings of a single treatment.
Our most-read article of 2020 concerned the discovery that an abnormal uptake of metals — from chromium to zinc — during childhood is associated with ALS in adults.
By analyzing teeth samples from 36 ALS patients and 31 unaffected people with a powerful technology, the researchers were able to establish and assess differences in temporal profiles of metal exposure. They found that ALS patients had greater exposure to several metals at various developmental stages, starting as early as birth.
These findings were confirmed in mouse models of ALS, both in their teeth and in their brains, suggesting that abnormal metal metabolism may contribute to several molecular changes that could increase the susceptibility of motor neurons to premature damage.
While deficiencies and excess of essential elements and toxic metals are known to contribute to ALS, researchers were now able to provide an idea of when these metabolic abnormalities start. The results also suggested that metal metabolism could be a viable therapeutic target to prevent or halt ALS.
At ALS News Today, we hope these stories and our reporting throughout 2021 help to better inform and improve the lives of everyone affected by ALS.
We wish all our readers a happy 2021.
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